Circulating Cell Free DNA Integrity Index as a Biomarker for Response to Chemotherapy in Patients with Metastatic Colorectal Carcinoma.

OBJECTIVE: Assessing plasma Cell Free DNA (cfDNA) integrity index as a biomarker for response prediction and early response evaluation in mCRC patients receiving chemotherapy, in comparison to Carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9), to be used as an additional tool to computed tomography (CT). METHODS: CEA, CA19-9, cfDNA concentration and cfDNA integrity index (ALU 247/115) measurements were conducted on 86 subjects divided into 43 healthy volunteers and 43 mCRC patients, before starting chemotherapy and then after 6-12 weeks of therapy initiation (3-4 cycles FOLFOX) at first response assessment. Plasma cfDNA integrity index was calculated as the ratio of long to short DNA fragments (ALU 247/115) amplified and detected by real-time PCR. Serum CEA and CA19-9 were measured by chemiluminescent immunometric assay. RESULTS: Baseline cfDNA integrity index was statistically significantly different between responders and non-responders (p=0.03). It was found that at cut off 0.608, sensitivity was 73.7%, specificity was 66.7% and diagnostic accuracy=69.77%. Markers with statistical significant difference between responders and non-responders after chemotherapy were CEA % change (p=0.035), CA19-9 (p=0.024), cfDNA integrity index (p=0.035) and cfDNA integrity index % change (p<0.001). Among these markers, cfDNA integrity index % change had the best sensitivity (84.2%), specificity (95.2%) and diagnostic accuracy (90.7%) at cut off -17.827%. CONCLUSION: Baseline cfDNA integrity index can be used as a potential marker to predict response to chemotherapy. cfDNA integrity index (ALU 247/115) % change rather than its absolute value is superior to CEA, CA19-9, cfDNA concentration and their % changes in early assessment of response to chemotherapy.

Serum Serotonin as a Potential Diagnostic Marker for Hepatocellular Carcinoma.

To assess the potential role of serum serotonin level in hepatocellular carcinoma (HCC) diagnosis. A case-control study that involved 100 Egyptian adults. Subjects were divided into 4 groups: Group I: 21 patients with late-stage HCC on top of liver cirrhosis, Group II: 28 patients with early-stage HCC on top of liver cirrhosis, Group III: 26 patients with cirrhosis with no evidence of HCC, and Group IV: 25 healthy age- and sex-matched subjects were as a control group. Serum serotonin level was determined in all recruited subjects using high-performance liquid chromatography-fluorescent detection method. Alpha-fetoprotein had a statistically significant elevation in group I with a median of 1300 ng/L (195-2544 ng/L) compared to groups II and III (P ≤ 0.01). Regarding serum serotonin level, it had a statistically significant elevation in group II with a median of 275 ng/µL (204.7-400 ng/µL) compared to groups I, III, and IV with median of 33 ng/µL (30-50 ng/µL), 50 ng/µL (30-60 ng/µL), and 102 (85-150 ng/µL), respectively (P = 0.001). Receiver operating characteristic curve showed that serum serotonin at cutoff value of 108 ng/µL had a sensitivity of 100% and specificity of 92.3% in discriminating early-stage HCC from cirrhosis. Serum serotonin level is a rapid, sensitive, noninvasive diagnostic biomarker for the detection of early-stage HCC.

Increased expression of serum periostin and YKL40 in children with severe asthma and asthma exacerbation.

Children with severe asthma or acute asthma exacerbation may encounter difficulties in performing pulmonary function tests. In this situation, serum biomarkers can play a great role in evaluation of such patients. The aim of this study was to estimate the serum levels of human chitinase-3-like protein 1 (YKL40) and periostin in a group of Egyptian children with asthma during acute asthma exacerbation and in stable asthmatics compared with healthy control, and to correlate these findings with the severity of asthma. This cross-sectional study enrolled 120 childrenwith asthma with different degrees of asthma severity, according to the Global Initiative for Asthma guidelines, along with 60 age-matched and sex-matched healthy control. A complete blood count and an estimation of serum periostin and YKL40 levels were performed for all cases and control. Individual and mean values of periostin and YKL40 were significantly higher during acute asthma exacerbations, p<0.001. A highly significant relation between serum levels of periostin and YKL40 and asthma severity, p value for each was <0.001. Absolute eosinophil count was significantly correlated with the serum periostin levels in stable asthmatic group (p=0.01) only. There was significantly positive correlation (P<0.001) between both markers in stable asthmatic group. Spearman's correlation coefficient shows a statistically significant positive correlation between both markers and patient's age and duration of asthma, p value for each was 0.001. These findings highlight the importance of periostin and YKL40 as serum biomarkers for assessment of asthma severity and acute asthma exacerbations in children with asthma.

Altered expression of WFS1 and NOTCH2 genes associated with diabetic nephropathy in T2DM patients.

AIM: The increased incidence of type 2 diabetes mellitus (T2DM) and the importance of early identification and management of its complications, especially diabetic nephropathy (DN), have spotted the light on genetic factors that increase risk of T2DM and its related nephropathy. The present study aimed at investigating expression of (KCNJ11, ABCC8, JAZF1, WFS1, PPARG, NOTCH2 and EXOSC4) genes in peripheral blood of T2DM patients. METHOD: The study included 30 non-complicated T2DM patients, 30 patients with DN and 40 healthy controls. Quantitative Real Time PCR Array was used to study gene expression. RESULTS: NOTCH2 showed higher expression while KCNJ11, JAZF1, WFS1 and PPARG genes showed lower expression in DN patients compared to non-complicated patients. KCNJ11, JAZF1, WFS1, PPARG, and EXOSC4 expression showed significant negative correlation with microalbumin, while NOTCH2 expression was significantly positively correlated with microalbumin. AS regard HbA1c and studied genes expression, there was significant negative correlation between WFS1 expression and HbA1c, while NOTCH2, KCNJ11, JAZF1, PPARG, EXOSC4 expression didn't show significant correlation with HbA1c. Risk ratio of studied genes expression showed that WFS1 and NOTCH2 had highest risk ratio (30) and highest sensitivity and specificity, in relation to DN and they were the best predictors in the group of studied genes at cut off value of ≤0.861 for WFS1 and ≥0.678 for NOTCH2. CONCLUSION: Altered expression of WFS1 and NOTCH2 genes may play a role in pathogenesis and development of DN in patients with T2DM. These results may contribute in early identification and management of DN.

Diagnostic indicator of acute lung injury for pediatric critically ill patients at a tertiary pediatric hospital.

Early identification of acute lung injury (ALI) in pediatric patients at risk of mortality is important for improving outcome.Assessment of soluble form of receptor for advanced glycation end products (sRAGE) as a valid biomarker for diagnosis of ALI among critically ill, pediatric patients in addition to correlating levels of sRAGE and different outcomes of those patients.A Hospital-based case-control study was conducted in pediatric intensive care units (PICUs) at Cairo University Hospital, along a period of 6 months. Total of 68 pediatric patients following inclusion criteria were classified into: patients with ALI; with both ALI and sepsis; with sepsis and control patients. They were prospectively followed and their laboratory and immunological workup (at days 1 and 9) was done to measure serum sRAGE levels and detect (sRAGE) genotypes.The age of the included children ranged from 8 to 84 months. Plasma level of sRAGE was significantly higher in plasma from patients with ALI regardless of associated sepsis. Plasma sRAGE levels were positively correlated with lung injury score. When assessing sRAGE genotypes, TA and TT genotypes were significant in most of the ALI with and without sepsis patients.Monitoring levels of sRAGE and genotypes can significantly affect the survival of ALI children.

Angiotensin-converting enzyme gene polymorphisms and hypertension in occupational noise exposure in Egypt.

BACKGROUND: The gene-environment interaction in the pathogenesis of hypertension has not been extensively studied in occupational noise. OBJECTIVES: The aim of this study was to determine the relationship between noise and hypertension in Egyptian workers, the interaction of angiotensin-converting enzyme (ACE) gene polymorphisms as modifiers, and the possible relationship between noise hearing impairment and hypertension. METHODS: Study subjects were divided into two groups depending on noise exposure level. The control group (n = 161) was exposed to noise intensity <85 dB and the exposed group (n = 217) was exposed to noise intensity ≧85 dB. A polymerase chain reaction was used to differentiate the various genotypes of ACE insertion/deletion (I/D) and ACE G2350A. RESULTS: Noise significantly increased the likelihood of hypertension. Carriers of the genotypes AG, GG, and DD were vulnerable to hypertension on noise exposure. No association between hypertension and hearing impairment or noise-induced hearing loss (NIHL) was found. CONCLUSION: Our results support the association between ACE gene polymorphisms and occurrence of hypertension in noise-exposed workers.